Fat Soluble vitamins affect composition of extracellular matrix deposited by human aortic smooth muscle and endothelial cells in vitro

Ivanov V, Ivanova S, Niedzwiecki A, Rath M

Current Topics in Nutraceutical Research; 19(1), 36-45, doi: https://doi.org/10.37290/ctnr2641-452X.19:36–45

Abstract:

Vascular calcification is a pathophysiological process that is associated with coronary atherosclerosis, and is a prognostic marker of cardiovascular morbidity and mortality. The process of arterial wall calcification is triggered and accompanied by pro-osteogenic phenotypical modifications of resident smooth muscle cells (SMC). Vitamin C (ascorbic acid) is an essential nutrient required to support the production of extracellular matrix components and maintain healthy connective tissue. In this study we investigated the effects of ascorbic acid on cultured human aortic SMC calcification process in vitro. Our results demonstrate that supplementation of SMC cultures with ascorbic acid significantly decreases calcium accumulation in SMC-produced and -deposited extracellular matrix. These effects were accompanied by a reduction in cell-associated alkaline phosphatase activity. Significantly, treatment of cultured SMC with HMG-CoA reductase inhibitors, simvastatin and mevastatin, resulted in increased calcium accumulation in cultured SMC.

Read more: Fat Soluble vitamins affect composition of extracellular matrix deposited by human aortic smooth muscle and endothelial cells in vitro

Vitamin C inhibits the calcification process in human vascular smooth muscle cells

Ivanov V, Ivanova S, Niedzwiecki A, Rath M

Am J Cardiovasc Dis. 2020; 10(2): 108–116.

Abstract:

Atherosclerotic cardiovascular disease is accompanied by changes in arterial connective tissue. We evaluated the effects of fat-soluble vitamins A, D, and E individually and in combinations on the composition of extracellular matrix produced and deposited by arterial wall cells, human aortic smooth muscle cells, and endothelial cells. Individually, vitamins D and E stimulated collagen type I extracellular matrix deposition in human aortic smooth muscle cell cultures. However, vitamins A, D, and E reduced collagen type IV deposition by human aortic smooth muscle cell, counteracting the stimulatory effects of vitamin C.…

Read more: Vitamin C inhibits the calcification process in human vascular smooth muscle cells

Beneficial metabolic effects of Vitamin D on arterial wall cells in vitro

V. Ivanov, S.Ivanova, A. Niedzwiecki, M. Rath

Journal of Cellular Medicine and Natural Health, July 2019

 

In recent years, many studies have shown positive effects of vitamin D on health, including various benefits to inflammation and immune response, cognitive function, protection against metabolic syndrome and cardiovascular disease. Vitamin D deficiency has been closely related to the development of coronary heart disease and its mortality.Vitamin D involvement in mitigating the pathogenesis and progression of CHD may occur at different levels, such as by regulation of renin-angiotensin system to lower blood pressure, promotion of insulin secretion, decrease in insulin resistance, regulation of cell differentiation andproliferation, and anti-inflammatory and anti-atherosclerosis effects, but the specific mechanisms have not yet been fully defined.…

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Cardiovascular Effects of Cyclical Dietary Vitamin C Withdrawal in Mice Deficient in Internal Synthesis of Vitamin C and producing human lipoprotein (a): Gulo(-/-); Lp(a)+

Lei Shi, Aleksandra Niedzwiecki, Vadim Ivanov and Matthias Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Int J Cardiovasc Res 2018, 7:6 DOI: 10.4172/2324-8602.1000397

Abstract:

Background: Scientific knowledge of the impact of periodic dietary vitamin C intake and withdrawal on the development of cardiovascular disease has been limited. Our earlier study using a transgenic Gulo(-/-); Lp(a)+ mouse model mimicking human metabolism in respect to a lack of internal synthesis of vitamin C and expression of human lipoprotein (a) [Lp(a)], a recognized risk factor for cardiovascular disease, showed that vitamin C deficiency triggers vascular deposition of Lp(a) and atherosclerosis. In this study we used this mouse model to investigate the effect of cyclical vitamin C withdrawal and its continuous supplementation on metabolic factors related to cardiovascular health, such as lipid profile and vascular plaque development.…

Read more: Cardiovascular Effects of Cyclical Dietary Vitamin C Withdrawal in Mice Deficient in Internal Synthesis of Vitamin C and producing human lipoprotein (a): Gulo(-/-); Lp(a)+

Effects of Various Multi-Nutrient Supplements on the Production and Extracellular Deposition of Collagen I and IV by Human Aortic Smooth Muscle Cells

Vadim Ivanov, M.D., Ph.D., Svetlana Ivanova, M.D., Aleksandra Niedzwiecki, Ph.D. and Matthias Rath, M.D.
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Journal of Cellular Medicine and Natural Health (August 2018)

Abstract:

Chronic vitamin deficiency is an underlying cause of many modern human chronic diseases, including cardiovascular disease (CVD).1 A major pathological mechanism leading to the development of CVD is loss of vascular-wall integrity, a structural weakness that triggers the atherosclerotic process.2 The arterial wall is composed of the constituent cells and surrounding extracellular matrix (ECM).3…

Read more: Effects of Various Multi-Nutrient Supplements on the Production and Extracellular Deposition of Collagen I and IV by Human Aortic Smooth Muscle Cells

Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice

John Cha, Aleksandra Niedzwiecki, Matthias Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
American Journal of Cardiovascular Medicine 2015;5(1):53-62

www.AJCD.us /ISSN:2160-200X/AJCD0007056

Abstract: Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals.…

Read more: Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice

Inhibition Of Collagen Synthesis By Select Calcium And Sodium Channel Blockers Can Be Mitigated By Ascorbic Acid And Ascorbyl Palmitate

V. Ivanov, S. Ivanova, T. Kalinovsky, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
American Journal of Cardiovascular Medicine 6(2):26-35, 2016

Abstract: Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction.…

Read more: Inhibition Of Collagen Synthesis By Select Calcium And Sodium Channel Blockers Can Be Mitigated By Ascorbic Acid And Ascorbyl Palmitate

A Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Extract Suppresses Autocrine Inflammatory Response in Cultured Human Aortic Smooth Muscle Cells

V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Research Communications in Molecular Pathology and Pharmacology 2004

Introduction:
Recognition of the involvement of inflammatory processes in atherosclerotic lesion initiation and development of pathological consequences initiated a search for an effective inhibitor. Naturally occurring compounds demonstrate a wider spectrum of biological activity and fewer side effects than synthetic drugs. Mixtures of natural compounds often produce synergistically enhanced therapeutic action.…

Read more: A Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Extract Suppresses Autocrine Inflammatory Response in Cultured Human Aortic Smooth Muscle Cells

Bioflavonoids Effectively Inhibit Smooth Muscle Cell-Mediated Contraction of Collagen Matrix Induced by Angiotensin II

V. Ivanov, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
The Journal of Cardiovascular Pharmacology 2005, 46(5): 570-6

Introduction:
Plant-derived bioflavonoids have been recognized to support arterial wall structural integrity and interfere with a variety of pro-atherosclerotic stimuli. In this study we tested the effects of bioflavonoids on the contractile activity of cultured human aortic smooth muscle cells (SMC) embedded in a three-dimensional type I collagen matrix.…

Read more: Bioflavonoids Effectively Inhibit Smooth Muscle Cell-Mediated Contraction of Collagen Matrix Induced by Angiotensin II

Enhancement of Cardio-Protective Effects and Attenuation of Adverse Effects of Female Sex Hormones on Cultured Human Vascular Smooth Muscle Cells by a Combination of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Epigallocatechin Gallate

V.Ivanov, S. Ivanova, W. Roomi, T.Kalinovsky, A. Niedzwiecki, M.Rath
Journal of the American Neutraceutical Association 2005, 8(1): 46-51

In this in vitro study, the effects of adjunctive use of a formulation containing ascorbic acid, lysine, proline, arginine, N-acetyl cysteine, and epigallocatechin gallate (NS) with female sex hormones was tested on human aortic smooth muscle cells (SMC). Estradiol and progesterone stimulated DNA synthesis in SMC 30% and 24% respectively at 25-150 nmol/L concentrations. NS (20 µg/ml) inhibited SMC growth by 30% over the control and reversed the stimulatory effect of the sex hormones to a maximum of 25% inhibition. Dehydroepiandrosterone sulfate (DHEAS) inhibited SMC growth by 50% at 0.1 mmol/L. Addition of NS enhanced the DHEAS inhibitory effect to 70% as compared to the control.…

Read more: Enhancement of Cardio-Protective Effects and Attenuation of Adverse Effects of Female Sex Hormones on Cultured Human Vascular Smooth Muscle Cells by a Combination of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Epigallocatechin Gallate

Extracellular Matrix-Mediated Control of Aortic Smooth Muscle Growth and Migration by a Combination of Ascorbic Acid, Lysine, Proline, and Catechins

V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2007, 50(5): 541-547

Extracellular matrix (ECM) function and structure are severely compromised at atherosclerotic lesion sites, contributing to initiation and progression of the disease. This study investigated whether ECM biological properties would be beneficially affected by exposure to nutrients essential for collagen synthesis and posttranslational modification. Confluent layers of human aortic smooth muscle cells (SMC) grown on collagen substrate were cultured in the presence of the tested compounds for 7 to 10 days. Pretreated cells were removed from the ECM surface by differential treatment and replaced with secondary innocent SMC cultures.…

Read more: Extracellular Matrix-Mediated Control of Aortic Smooth Muscle Growth and Migration by a Combination of Ascorbic Acid, Lysine, Proline, and Catechins

Anti-Atherogenic Effects of a Mixture of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Phenolics in Human Aortic Smooth Muscle Cells

V. Ivanov, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2007, 49(3): 140-145.

Certain drastic behavioral modifications by arterial wall smooth muscle cells (SMC) have been considered key steps in the formation of atherosclerotic lesions: massive migration of SMC from the media to the intima layer of the vessel, dedifferentiation of SMC to proliferating phenotype, and increased secretion of inflammatory cytokines as a response to inflammatory stimuli. We investigated the anti-atherogenic effects of naturally occuring compounds (ascorbic acid, green tea extract, lysine, proline, arginine, and N-acetyl cysteine) using the model of cultured aortic SMC. Cell growth was measured by DNA synthesis, cell invasiveness was measured through Matrigel, matrix metalloproteinase-2 (MMP-2) secretion was measured by zymography, and SMC secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) was measured by immunochemistry. Fetal bovine serum-stimulated SMC growth was inhibited by the nutrient mixture (NM) with 85% inhibition at 100 µg/mL.…

Read more: Anti-Atherogenic Effects of a Mixture of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Phenolics in Human Aortic Smooth Muscle Cells

Plant-Derived Micronutrients Suppress Monocyte Ahesion to Cultured Human Aortic Endothelial Cell Layer by Modulating Its Extracellular Matrix Composition

V. Ivanov, S. Ivanova, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2008, 52: 55-65

Abstract
Monocyte adhesion to endothelium plays an important role in atherosclerosis. We investigated the effects of micronutrients on monocyte-binding properties of extracellular matrix (ECM) produced by human aortic endothelial cells (AoEC). Confluent cultures of AoEC were exposed to ascorbic acid, quercetin, gotu kola extract (10% asiatic acid), green tea extract (40% epigallocatechin gallate), or a mixture of these micronutrients for 48 hourss. AoEC-produced ECM was exposed by differential treatment. U937 monocyte adhesion was assayed by fluorescence. ECM composition was assayed immunochemically and with radiolabeled metabolic precursors. AoEC exposure to micronutrients reduced ECM capacity to bind monocytes in a dose-dependent manner.…

Read more: Plant-Derived Micronutrients Suppress Monocyte Ahesion to Cultured Human Aortic Endothelial Cell Layer by Modulating Its Extracellular Matrix Composition

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